摘要
目的:探究克癀胶囊对高脂高糖饮食诱导的非酒精性脂肪性肝炎(NASH)小鼠模型的治疗作用。方法:将60只雄性C57/BL6小鼠随机分为正常组(Ctrl组)、模型组(HFHS组)、克癀胶囊低、中、高剂量组(KL、KM、KH组)和奥贝胆酸组(OCA组),采用高脂饮食高糖饮水12周诱导NASH模型,第13周开始各组小鼠给予相应药物,持续给药6周,观察小鼠形态、体重及进食量、肝重/体重比指数、肝组织甘油三酯(TG)含量、肝组织HE染色和油红O染色及非酒精性脂肪肝活动评分(NAS)、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和γ谷氨酰转肽酶(GGT)活性、血清TG、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及血清游离脂肪酸(FFA)含量、空腹血糖(FBG)、空腹胰岛素(FINS)含量和胰岛素抵抗指数(HOMA-IR)。结果:与Ctrl组相比,HFHS组小鼠体型肥胖,肝脏变大,肝重显著升高,肝脏TG含量,血清ALT、AST活性,血清TC、LDL-C、HDL-C、FINS、FBG含量及HOMA-IR均显著升高(P<0.01),血清FFA含量显著降低(P<0.05)。肝组织HE染色见肝细胞脂肪变性明显,出现炎性细胞浸润,部分肝细胞出现气球样变,肝组织NAS评分显著升高(P<0.01),油红O染色可见明显红色脂滴。与HFHS组相比,KL、KM、KH组小鼠肝组织TG含量显著下降(P<0.05);KM、KL、KH组小鼠肝组织脂肪变性、小叶内炎症、气球样变均显著减少,肝组织NAS评分显著下降(P<0.05),油红O染色脂滴减少。KL组小鼠血清ALT和AST活性及血清TC、HDL-C含量显著降低(P<0.05),血清TG、FFA含量显著上升(P<0.05);KM组小鼠血清HDL-C及FBG水平显著降低(P<0.05);KH组小鼠血清ALT活性、血清TC、HDL-C、LDL-C及FBG水平显著降低(P<0.05)。结论:克癀胶囊低、中、高剂量组(0.5 g/kg、1 g/kg、2 g/kg,分别相当于临床剂量的6.17、12.33、24.66倍)对高脂饮食高糖饮水诱导的小鼠非酒精性脂肪性肝炎均具有不同程度的治疗作用,且对肝脏TG含量的改善作用具有剂量依赖性趋势。
Objective:To explore the therapeutic effect of Ke Huang capsule on non-alcoholic steatohepatitis(NASH)mouse model induced by high-fat and high-sugar diet.Methods:A total of sixty C57/BL6 mice were randomly divided into normal group(Ctrl group),model group(HFHS group),low,medium and high dose of Ke Huang capsule groups(KL,KM and KH groups)and obeticholic acid group(OCA group).The NAFLD model was induced by high fat diet and high sugar drinking water for 12 weeks.The morphology,body weight and food intake of mice were observed.The liver weight/body weight ratio index,liver triglyceride(TG)content,HE staining and oil red O staining of liver tissue and non-alcoholic fatty liver activity score(NAS)were performed.The serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)andγ-glutamyl transpeptidase(GGT)activities,serum triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and serum free fatty acid(FFA),fasting blood glucose(FBG),fasting insulin(FINS)and insulin resistance index(HOMA-IR)were measured.Results:Compared with the Ctrl group,the mice in the HFHS group were obese,the liver was larger,the liver weight was significantly increased,the liver TG content,serum ALT and AST activities,serum TC,LDL-C,HDL-C,FINS,FBG contents and HOMA-IR were significantly increased(P<0.01),serum FFA level decreased significantly(P<0.05).The HE staining of liver tissue showed obvious hepatocyte steatosis,inflammatory cell infiltration,balloon-like changes in some hepatocytes,and a significant increase in liver tissue NAS score(P<0.01),and oil red O staining showed obvious red lipid droplets.Compared with HFHS group,TG content in liver tissue of KL,KM and KH groups decreased significantly(P<0.05);The steatosis,lobular inflammation and ballooning of liver tissue in KM,KL and KH groups were significantly reduced,and the NAS score of liver tissue was significantly decreased(P<0.05),oil red O-stained lipid droplets decreased.The serum ALT and AST activities and serum TC and HDL-C contents in KL group were significantly decreased(P<0.05),serum TG and FFA levels increased significantly(P<0.05).The levels of serum HDL-C and FBG in KM group were significantly decreased(P<0.05).KH group mice serum ALT activity,serum TC,HDL-C,LDL-C and FBG levels were significantly decreased(P<0.05).Conclusion:The low,medium and high dose groups(0.5 g/kg,1 g/kg,2 g/kg,respectively,equivalent to 6.17,12.33,24.66 times of the clinical dose)of Ke Huang capsule had different degrees of therapeutic effects on mice with non-alcoholic steatohepatitis induced by high-fat diet and high-sugar drinking water.The improvement of liver TG content has a dose-dependent trend,but the serum triglyceride and free fatty acid have an increasing effect on the capsule.
作者
李晓静
刘雅茹
李冉
涂天智
胡义扬
LI Xiao-jing;LIU Ya-ru;LI Ran;Tu Tian-zhi;HU Yi-yang(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine(Shanghai,201203),China)
出处
《中西医结合肝病杂志》
CAS
2024年第3期230-235,共6页
Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases
基金
上海中医药大学附属曙光医院横向课题(No.3936)。
关键词
非酒精性脂肪性肝炎
克癀胶囊
药效学
non-alcoholic steatohepatitis
Ke Huang capsule
pharmacodynamics
